Synergism Between -Terpineol and Terpinen-4-ol Potentiates Antivirulence Response Against Pseudomonas aeruginosa

Antivirulence strategies have emerged as next-generation therapies that are now becoming refractory to the use of traditional antimicrobial approaches. Considering the global medical burden associated with Pseudomonas aeruginosa infections, there is a pressing need to explore therapeutic alternatives. In this direction, the current study was aimed at investigating the combinational effects of alpha-terpineol (alpha-T) and terpinen-4-ol (T-4-ol), the principal bioactive components of tea tree oil, against P. aeruginosa. The phytochemical combination was examined for synergistic interaction and various biological properties, including antibacterial, quorum quenching (QQ), and antivirulence potential. alpha-T and T-4-ol displayed synergism and harbored profuse antibacterial properties against P. aeruginosa. The phytochemicals inhibited quorum sensing (QS) in biosensor strains of Agrobacterium tumefaciens and Chromobacterium violaceum by suppressing lacZ and diminishing violacein production, respectively. Moreover, alpha-T and T-4-ol, independently and in combination, extended antivirulence response by significantly reducing hemolysin, pyocyanin, pyochelin, and total protease production in P. aeruginosa PAO1 and PA14. Hence, this study suggests that the phytochemical combination of alpha-T and T-4-ol can be used as a potent antivirulence elixir over antibiotics to combat P. aeruginosa.